medwireNews: Results from a meta-analysis support use of immune checkpoint inhibitors (ICIs) for the treatment of sarcomatoid renal cell carcinoma (RCC).
The researchers found that ICI combinations improved both progression-free and overall survival by more than 40% versus treatment with the small-molecule tyrosine kinase inhibitor sunitinib.
“[Sarcomatoid] RCC represents a relatively rare form of RCC marked by aggressive biology, very poor prognosis and little benefit from anti-angiogenic agents,” say Roberto Iacovelli (Fondazione Policlinico Universitario A Gemelli, Rome, Italy) and co-authors in the European Journal of Cancer.
They add: “Current guidelines for the management of patients with [sarcomatoid] RCC are mainly borrowed from data available for [clear cell] RCC. Therefore, currently unmet clinical needs of the [sarcomatoid] RCC population need to be urgently addressed to improve patient outcomes.”
Combinations of anti-PD1 and anti-CTLA-4 agents have been shown to be effective for treating clear cell RCC, and patients with sarcomatoid differentiation were included in clinical trials of these drugs. Therefore, Iacovelli and colleagues were able to identity 467 such patients from four randomized, phase 3 studies.
Of the patients included in their meta-analysis, 226 were treated with combinations of ICIs – nivolumab plus ipilimumab, pembrolizumab plus axitinib, atezolizumab plus bevacizumab, and avelumab plus axitinib – and 241 received sunitinib and were used as controls in the analysis.
Patients in the ICI group had significantly improved progression-free (hazard ratio [HR]=0.56) and overall survival (HR=0.56) compared with those in the sunitinib group.
The objective response rate was also higher among ICI-treated patients than those given sunitinib, at 52.6% versus 20.7% (relative risk=2.53). A complete response to therapy was more than eight times more frequent in the ICI group, occurring in 26 patients (11.5%) treated with ICIs compared with only two (0.8%) treated with sunitinib.
Moreover, when the researchers compared progression-free survival in the patients with the sarcomatoid subgroup with that of the larger, overall population of patients with the clear cell subtype they found the sarcomatoid subgroup did significantly better (HR=0.73).
“Our data support the utility of ICI-based regimens for [sarcomatoid] RCC therapy, redefining the first-line treatment,” write the authors.
“However, many questions remain unsolved, underlining the need of further efforts to understand the biology of [sarcomatoid] RCC development and progression to identify potential specific targets for therapy to improve the poor prognosis of those patients,” they conclude.
By Helen Albert
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Eur J Cancer 2020; 136: 195–203